This project has concentrated on examining the electrophysiological and neuropharmacological bases for drug action using an in vitro model system, mammalian neurons grown in primary dissociated tissue culture. We have focused on the post-synaptic neuropharmacology and mechanism of action of: 1) the inhibitory neutral amino acids (gamma-aminobutyric acid (GABA), beta-alanine (BALA), glycine (GLY)) and the excitatory acidic amino acid (glutamic acid (GLU)), 2) the pharmacological convulsants (penicillin (PCN), pentylenetetrazol (PTZ), picrotoxin (PTX), bicuculline (BICUC)), 3) various clinically useful anticonvulsants (phenobarbital, diazepam, chlordiazepoxide) and 4) barbiturate anesthetics (pentobarbital). The primary observations are: 1) the response to iontophoresed inhibitory amino acids is a cooperative event requiring more than one amino acid while the excitatory amino acid glutamate requires only one molecule of amino acid per receptor, 2) convulsants produce paroxysmal depolarizing shifts (PDS) when added to the bathing medium and specifically block GABA or GLY mediated post-synaptic inhibition, 3) anticonvulsants block the development of or eliminate PDS produced by convulsant agents, and specifically augment GABA-mediated post-synaptic inhibition and 4) barbiturate anesthetics also augment GABA-mediated post-synaptic inhibition but, in addition, are able to directly operate the GABA receptor-coupled conductance. The latter mechanism may provide the basis for barbiturate anesthesia. BIBLIOGRAPHIC REFERENCES: Ransom, B. R. and Barker, J. L. Pentobarbital selectively enhances GABA-mediated post-synaptic inhibition in tissue cultures mouse spinal neurons. Brain Res. 114: 530-535, 1976.